English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Desmosome architecture derived from molecular dynamics simulations and cryo-electron tomography

Sikora, M., Ermel, U. H., Seybold, A., Kunz, M., Calloni, G., Reitz, J., et al. (2020). Desmosome architecture derived from molecular dynamics simulations and cryo-electron tomography. Proceedings of the National Academy of Sciences of the United States of America, 117(44), 27132-27140. doi:10.1073/pnas.2004563117.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Sikora, Mateusz1, 2, Author              
Ermel, Utz H.3, 4, Author
Seybold, Anna3, 4, Author
Kunz, Michael3, 4, Author
Calloni, Giulia3, 5, Author
Reitz, Julian3, 4, Author
Vabulas, R. Martin6, Author
Hummer, Gerhard1, 3, Author              
Frangakis, Achilleas S., Author
Affiliations:
1Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society, ou_2068292              
2Faculty of Physics, University of Vienna, Vienna, Austria, ou_persistent22              
3Buchmann Institute for Molecular Life Sciences, Frankfurt, Germany, ou_persistent22              
4Institute for Biophysics, Goethe University Frankfurt, Frankfurt, Germany, ou_persistent22              
5Institute for Biophysical Chemistry, Goethe University Frankfurt, Frankfurt, Germany, ou_persistent22              
6Institute of Biochemistry, Charité-Universitätsmedizin Berlin, Berlin, Germany, ou_persistent22              

Content

show
hide
Free keywords: cell–cell adhesion, cryo-electron tomography, desmosome, molecular dynamics simulations
 Abstract: Desmosomes are cell-cell junctions that link tissue cells experiencing intense mechanical stress. Although the structure of the desmosomal cadherins is known, the desmosome architecture-which is essential for mediating numerous functions-remains elusive. Here, we recorded cryo-electron tomograms (cryo-ET) in which individual cadherins can be discerned; they appear variable in shape, spacing, and tilt with respect to the membrane. The resulting sub-tomogram average reaches a resolution of ∼26 Å, limited by the inherent flexibility of desmosomes. To address this challenge typical of dynamic biological assemblies, we combine sub-tomogram averaging with atomistic molecular dynamics (MD) simulations. We generate models of possible cadherin arrangements and perform an in silico screening according to biophysical and structural properties extracted from MD simulation trajectories. We find a truss-like arrangement of cadherins that resembles the characteristic footprint seen in the electron micrograph. The resulting model of the desmosomal architecture explains their unique biophysical properties and strength.

Details

show
hide
Language(s): eng - English
 Dates: 2020-03-112020-09-012020-10-162020-11-03
 Publication Status: Published in print
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1073/pnas.2004563117
BibTex Citekey: sikora_desmosome_2020
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : Proc. Acad. Sci. USA
  Other : Proc. Acad. Sci. U.S.A.
  Other : Proceedings of the National Academy of Sciences of the USA
  Abbreviation : PNAS
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Washington, D.C. : National Academy of Sciences
Pages: - Volume / Issue: 117 (44) Sequence Number: - Start / End Page: 27132 - 27140 Identifier: ISSN: 0027-8424
CoNE: https://pure.mpg.de/cone/journals/resource/954925427230